Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19.

Temporal resolution of cellular features associated with a severe COVID-19 disease trajectory is needed for understanding skewed immune responses and defining predictors of outcome. Here, we performed a longitudinal multi-omics study using a two-center cohort of 14 patients. We analyzed the bulk transcriptome, bulk DNA methylome, and single-cell transcriptome (>358,000 cells, including BCR profiles) of peripheral blood samples harvested from up to 5 time points. Validation was performed in two independent cohorts of COVID-19 patients. Severe COVID-19 was characterized by an increase of proliferating, metabolically hyperactive plasmablasts. Coinciding with critical illness, we also identified an expansion of interferon-activated circulating megakaryocytes and increased erythropoiesis with features of hypoxic signaling. Megakaryocyte- and erythroid-cell-derived co-expression modules were predictive of fatal disease outcome. The study demonstrates broad cellular effects of SARS-CoV-2 infection beyond adaptive immune cells and provides an entry point toward developing biomarkers and targeted treatments of patients with COVID-19.

Relevance of Protein Intake for Weaning in the Mechanically Ventilated Critically Ill: Analysis of a Large International Database.

OBJECTIVES: The association between protein intake and the need for mechanical ventilation (MV) is controversial. We aimed to investigate the associations between protein intake and outcomes in ventilated critically ill patients. DESIGN: Analysis of a subset of a large international point prevalence survey of nutritional practice in ICUs. SETTING: A total of 785 international ICUs. PATIENTS: A total of 12,930 patients had been in the ICU for at least 96 hours and required MV by the fourth day after ICU admission at the latest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We modeled associations between the adjusted hazard rate (aHR) of death in patients requiring MV and successful weaning (competing risks), and three categories of protein intake (low: < 0.8 g/kg/d, standard: 0.8-1.2 g/kg/d, high: > 1.2 g/kg/d). We compared five different hypothetical protein diets (an exclusively low protein intake, a standard protein intake given early (days 1-4) or late (days 5-11) after ICU admission, and an early or late high protein intake). There was no evidence that the level of protein intake was associated with time to weaning. However, compared with an exclusively low protein intake, a standard protein intake was associated with a lower hazard of death in MV: minimum aHR 0.60 (95% CI, 0.45-0.80). With an early high intake, there was a trend to a higher risk of death in patients requiring MV: maximum aHR 1.35 (95% CI, 0.99-1.85) compared with a standard diet. CONCLUSIONS: The duration of MV does not appear to depend on protein intake, whereas mortality in patients requiring MV may be improved by a standard protein intake. Adverse effects of a high protein intake cannot be excluded.

Vitamin C in critical illness: end of the story or still a place?

PURPOSE OF REVIEW: Critical illness is associated with decreased micronutrient levels, including vitamin C, an essential antioxidant for systemic inflammation. This review discusses the most recent evidence of high-dose vitamin C monotherapy in critically ill adults. RECENT FINDINGS: Three randomized-controlled trials (RCTs) were published in 2022. A pilot study including 40 patients with septic shock could not detect significant differences in outcome parameters after administering vitamin C. A multicenter study with 124 septic patients showed no significant difference in 28-day mortality, while vitamin C was associated with an increased risk of acute kidney dysfunction. The LOVIT trial, an international prospective RCT in 872 septic patients, revealed an increased risk of the composite endpoint persistent organ dysfunction plus death at day 28 in the high-dose vitamin C group. Six systematic reviews and meta-analyses (SRMA), including up to 4740 patients published before and 2 SRMA publications including these RCTs showed divergent results on clinical endpoints including mortality. SUMMARY: The use of high-dose intravenous vitamin C cannot be recommended for the septic critically ill in clinical practice since the LOVIT trial. Further research is needed to evaluate its potential role in other critically ill patients.

German Patient Blood Management Network: effectiveness and safety analysis in 1.2 million patients.

BACKGROUND: Patient Blood Management (PBM) is a patient-centred, systematic, evidence-based approach to improve patient outcomes by managing and preserving a patient's own blood whilst promoting patient safety and empowerment. The effectiveness and safety of PBM over a longer period have not yet been investigated. METHODS: We performed a prospectively designed, multicentre follow-up study with non-inferiority design. Data were retrospectively extracted case-based from electronic hospital information systems. All in-hospital patients (≥18 yr) undergoing surgery and discharged between January 1, 2010 and December 31, 2019 were included in the analysis. The PBM programme focused on three domains: preoperative optimisation of haemoglobin concentrations, blood-sparing techniques, and guideline adherence/standardisation of allogeneic blood product transfusions. The outcomes were utilisation of blood products, composite endpoint of in-hospital mortality and postoperative complications (myocardial infarction/ischaemic stroke/acute renal failure with renal replacement therapy/sepsis/pneumonia), anaemia rate at admission and discharge, and hospital length of stay. RESULTS: A total of 1 201 817 (pre-PBM: n=441 082 vs PBM: n=760 735) patients from 14 (five university/nine non-university) hospitals were analysed. Implementation of PBM resulted in a substantial reduction of red blood cell utilisation. The mean number of red blood cell units transfused per 1000 patients was 547 in the PBM cohort vs 635 in the pre-PBM cohort (relative reduction of 13.9%). The red blood cell transfusion rate was significantly lower (P<0.001) with odds ratio 0.86 (0.85-0.87). The composite endpoint was 5.8% in the PBM vs 5.6% in the pre-PBM cohort. The non-inferiority aim (safety of PBM) was achieved (P<0.001). CONCLUSIONS: Analysis of >1 million surgical patients showed that the non-inferiority condition (safety of Patient Blood Management) was fulfilled, and PBM was superior with respect to red blood cell transfusion. CLINICAL TRIAL REGISTRATION: NCT02147795.

Protein intake and outcome of critically ill patients: analysis of a large international database using piece-wise exponential additive mixed models.

BACKGROUND: Proteins are an essential part of medical nutrition therapy in critically ill patients. Guidelines almost universally recommend a high protein intake without robust evidence supporting its use. METHODS: Using a large international database, we modelled associations between the hazard rate of in-hospital death and live hospital discharge (competing risks) and three categories of protein intake (low: < 0.8 g/kg per day, standard: 0.8-1.2 g/kg per day, high: > 1.2 g/kg per day) during the first 11 days after ICU admission (acute phase). Time-varying cause-specific hazard ratios (HR) were calculated from piece-wise exponential additive mixed models. We used the estimated model to compare five different hypothetical protein diets (an exclusively low protein diet, a standard protein diet administered early (day 1 to 4) or late (day 5 to 11) after ICU admission, and an early or late high protein diet). RESULTS: Of 21,100 critically ill patients in the database, 16,489 fulfilled inclusion criteria for the analysis. By day 60, 11,360 (68.9%) patients had been discharged from hospital, 4,192 patients (25.4%) had died in hospital, and 937 patients (5.7%) were still hospitalized. Median daily low protein intake was 0.49 g/kg [IQR 0.27-0.66], standard intake 0.99 g/kg [IQR 0.89- 1.09], and high intake 1.41 g/kg [IQR 1.29-1.60]. In comparison with an exclusively low protein diet, a late standard protein diet was associated with a lower hazard of in-hospital death: minimum 0.75 (95% CI 0.64, 0.87), and a higher hazard of live hospital discharge: maximum HR 1.98 (95% CI 1.72, 2.28). Results on hospital discharge, however, were qualitatively changed by a sensitivity analysis. There was no evidence that an early standard or a high protein intake during the acute phase was associated with a further improvement of outcome. CONCLUSIONS: Provision of a standard protein intake during the late acute phase may improve outcome compared to an exclusively low protein diet. In unselected critically ill patients, clinical outcome may not be improved by a high protein intake during the acute phase. Study registration ID number ISRCTN17829198.

Administration of vitamin D and its metabolites in critically ill adult patients: an updated systematic review with meta-analysis of randomized controlled trials.

BACKGROUND: The clinical significance of vitamin D administration in critically ill patients remains inconclusive. The purpose of this systematic review with meta-analysis was to investigate the effect of vitamin D and its metabolites on major clinical outcomes in critically ill patients, including a subgroup analysis based on vitamin D status and route of vitamin D administration. METHODS: Major databases were searched through February 9, 2022. Randomized controlled trials of adult critically ill patients with an intervention group receiving vitamin D or its metabolites were included. Random-effect meta-analyses were performed to estimate the pooled risk ratio (dichotomized outcomes) or mean difference (continuous outcomes). Risk of bias assessment included the Cochrane tool for assessing risk of bias in randomized trials. RESULTS: Sixteen randomized clinical trials with 2449 patients were included. Vitamin D administration was associated with lower overall mortality (16 studies: risk ratio 0.78, 95% confidence interval 0.62-0.97, p = 0.03; I2 = 30%), reduced intensive care unit length of stay (12 studies: mean difference - 3.13 days, 95% CI - 5.36 to - 0.89, n = 1250, p = 0.006; I2 = 70%), and shorter duration of mechanical ventilation (9 studies: mean difference - 5.07 days, 95% CI - 7.42 to - 2.73, n = 572, p < 0.0001; I2 = 54%). Parenteral administration was associated with a greater effect on overall mortality than enteral administration (test of subgroup differences, p = 0.04), whereas studies of parenteral subgroups had lower quality. There were no subgroup differences based on baseline vitamin D levels. CONCLUSIONS: Vitamin D supplementation in critically ill patients may reduce mortality. Parenteral administration might be associated with a greater impact on mortality. Heterogeneity and assessed certainty among the studies limits the generalizability of the results. TRIAL REGISTRATION: PROSPERO international prospective database of systematic reviews (CRD42021256939-05 July 2021).

Medical nutrition therapy and clinical outcomes in critically ill adults: a European multinational, prospective observational cohort study (EuroPN).

BACKGROUND: Medical nutrition therapy may be associated with clinical outcomes in critically ill patients with prolonged intensive care unit (ICU) stay. We wanted to assess nutrition practices in European intensive care units (ICU) and their importance for clinical outcomes. METHODS: Prospective multinational cohort study in patients staying in ICU ≥ 5 days with outcome recorded until day 90. Macronutrient intake from enteral and parenteral nutrition and non-nutritional sources during the first 15 days after ICU admission was compared with targets recommended by ESPEN guidelines. We modeled associations between three categories of daily calorie and protein intake (low: < 10 kcal/kg, < 0.8 g/kg; moderate: 10-20 kcal/kg, 0.8-1.2 g/kg, high: > 20 kcal/kg; > 1.2 g/kg) and the time-varying hazard rates of 90-day mortality or successful weaning from invasive mechanical ventilation (IMV). RESULTS: A total of 1172 patients with median [Q1;Q3] APACHE II score of 18.5 [13.0;26.0] were included, and 24% died within 90 days. Median length of ICU stay was 10.0 [7.0;16.0] days, and 74% of patients could be weaned from invasive mechanical ventilation. Patients reached on average 83% [59;107] and 65% [41;91] of ESPEN calorie and protein recommended targets, respectively. Whereas specific reasons for ICU admission (especially respiratory diseases requiring IMV) were associated with higher intakes (estimate 2.43 [95% CI: 1.60;3.25] for calorie intake, 0.14 [0.09;0.20] for protein intake), a lack of nutrition on the preceding day was associated with lower calorie and protein intakes (- 2.74 [- 3.28; - 2.21] and - 0.12 [- 0.15; - 0.09], respectively). Compared to a lower intake, a daily moderate intake was associated with higher probability of successful weaning (for calories: maximum HR 4.59 [95% CI: 1.5;14.09] on day 12; for protein: maximum HR 2.60 [1.09;6.23] on day 12), and with a lower hazard of death (for calories only: minimum HR 0.15, [0.05;0.39] on day 19). There was no evidence that a high calorie or protein intake was associated with further outcome improvements. CONCLUSIONS: Calorie intake was mainly provided according to the targets recommended by the active ESPEN guideline, but protein intake was lower. In patients staying in ICU ≥ 5 days, early moderate daily calorie and protein intakes were associated with improved clinical outcomes. Trial registration NCT04143503 , registered on October 25, 2019.

Omega-6 sparing effects of parenteral lipid emulsions-an updated systematic review and meta-analysis on clinical outcomes in critically ill patients.

BACKGROUND: Parenteral lipid emulsions in critical care are traditionally based on soybean oil (SO) and rich in pro-inflammatory omega-6 fatty acids (FAs). Parenteral nutrition (PN) strategies with the aim of reducing omega-6 FAs may potentially decrease the morbidity and mortality in critically ill patients. METHODS: A systematic search of MEDLINE, EMBASE, CINAHL and CENTRAL was conducted to identify all randomized controlled trials in critically ill patients published from inception to June 2021, which investigated clinical omega-6 sparing effects. Two independent reviewers extracted bias risk, treatment details, patient characteristics and clinical outcomes. Random effect meta-analysis was performed. RESULTS: 1054 studies were identified in our electronic search, 136 trials were assessed for eligibility and 26 trials with 1733 critically ill patients were included. The median methodologic score was 9 out of 14 points (95% confidence interval [CI] 7, 10). Omega-6 FA sparing PN in comparison with traditional lipid emulsions did not decrease overall mortality (20 studies; risk ratio [RR] 0.91; 95% CI 0.76, 1.10; p = 0.34) but hospital length of stay was substantially reduced (6 studies; weighted mean difference [WMD] - 6.88; 95% CI - 11.27, - 2.49; p = 0.002). Among the different lipid emulsions, fish oil (FO) containing PN reduced the length of intensive care (8 studies; WMD - 3.53; 95% CI - 6.16, - 0.90; p = 0.009) and rate of infectious complications (4 studies; RR 0.65; 95% CI 0.44, 0.95; p = 0.03). When FO was administered as a stand-alone medication outside PN, potential mortality benefits were observed compared to standard care. CONCLUSION: Overall, these findings highlight distinctive omega-6 sparing effects attributed to PN. Among the different lipid emulsions, FO in combination with PN or as a stand-alone treatment may have the greatest clinical impact. Trial registration PROSPERO international prospective database of systematic reviews (CRD42021259238).

Comparison of oscillometric, non-invasive and invasive arterial pressure monitoring in patients undergoing laparoscopic bariatric surgery - a secondary analysis of a prospective observational study.

BACKGROUND: Oscillometric, non-invasive blood pressure measurement (NIBP) is the first choice of blood pressure monitoring in the majority of low and moderate risk surgeries. In patients with morbid obesity, however, it is subject to several limitations. The aim was to compare arterial pressure monitoring by NIBP and a non-invasive finger-cuff technology (Nexfin®) with the gold-standard invasive arterial pressure (IAP). METHODS: In this secondary analysis of a prospective observational, single centre cohort study, systolic (SAP), diastolic (DAP) and mean arterial pressure (MAP) were measured at 16 defined perioperative time points including posture changes, fluid bolus administration and pneumoperitoneum (PP) in patients undergoing laparoscopic bariatric surgery. Absolute arterial pressures by NIBP, Nexfin® and IAP were compared using correlation and Bland Altman analyses. Interchangeability was defined by a mean difference ≤ 5 mmHg (SD ≤8 mmHg). Percentage error (PE) was calculated as an additional statistical estimate. For hemodynamic trending, concordance rates were analysed according to the Critchley criterion. RESULTS: Sixty patients (mean body mass index of 49.2 kg/m2) were enrolled and data from 56 finally analysed. Pooled blood pressure values of all time points showed a significant positive correlation for both NIPB and Nexfin® versus IAP. Pooled PE for NIBP versus IAP was 37% (SAP), 35% (DAP) and 30% (MAP), for Nexfin versus IAP 23% (SAP), 26% (DAP) and 22% (MAP). Correlation of MAP was best and PE lowest before induction of anesthesia for NIBP versus IAP (r = 0.72; PE 24%) and after intraoperative fluid bolus administration for Nexfin® versus IAP (r = 0.88; PE: 17.2%). Concordance of MAP trending was 90% (SAP 85%, DAP 89%) for NIBP and 91% (SAP 90%, DAP 86%) for Nexfin®. MAP trending was best during intraoperative ATP positioning for NIBP (97%) and at induction of anesthesia for Nexfin® (97%). CONCLUSION: As compared with IAP, interchangeability of absolute pressure values could neither be shown for NIBP nor Nexfin®, however, NIBP showed poorer overall correlation and precision. Overall trending ability was generally high with Nexfin® surpassing NIBP. Nexfin® may likely render individualized decision-making in the management of different hemodynamic stresses during laparoscopic bariatric surgery, particularly where NIBP cannot be reliably established. TRIAL REGISTRATION: The non-interventional, observational study was registered retrospectively at ( NCT03184285 ) on June 12, 2017.

Gastrointestinal dysfunction in the critically ill: a systematic scoping review and research agenda proposed by the Section of Metabolism, Endocrinology and Nutrition of the European Society of Intensive Care Medicine.

BACKGROUND: Gastrointestinal (GI) dysfunction is frequent in the critically ill but can be overlooked as a result of the lack of standardization of the diagnostic and therapeutic approaches. We aimed to develop a research agenda for GI dysfunction for future research. We systematically reviewed the current knowledge on a broad range of subtopics from a specific viewpoint of GI dysfunction, highlighting the remaining areas of uncertainty and suggesting future studies. METHODS: This systematic scoping review and research agenda was conducted following successive steps: (1) identify clinically important subtopics within the field of GI function which warrant further research; (2) systematically review the literature for each subtopic using PubMed, CENTRAL and Cochrane Database of Systematic Reviews; (3) summarize evidence for each subtopic; (4) identify areas of uncertainty; (5) formulate and refine study proposals that address these subtopics; and (6) prioritize study proposals via sequential voting rounds. RESULTS: Five major themes were identified: (1) monitoring, (2) associations between GI function and outcome, (3) GI function and nutrition, (4) management of GI dysfunction and (5) pathophysiological mechanisms. Searches on 17 subtopics were performed and evidence summarized. Several areas of uncertainty were identified, six of them needing consensus process. Study proposals ranked among the first ten included: prevention and management of diarrhoea; management of upper and lower feeding intolerance, including indications for post-pyloric feeding and opioid antagonists; acute gastrointestinal injury grading as a bedside tool; the role of intra-abdominal hypertension in the development and monitoring of GI dysfunction and in the development of non-occlusive mesenteric ischaemia; and the effect of proton pump inhibitors on the microbiome in critical illness. CONCLUSIONS: Current evidence on GI dysfunction is scarce, partially due to the lack of precise definitions. The use of core sets of monitoring and outcomes are required to improve the consistency of future studies. We propose several areas for consensus process and outline future study projects.

Meeting nutritional targets of critically ill patients by combined enteral and parenteral nutrition: review and rationale for the EFFORTcombo trial.

While medical nutrition therapy is an essential part of the care for critically ill patients, uncertainty exists about the right form, dosage, timing and route in relation to the phases of critical illness. As enteral nutrition (EN) is often withheld or interrupted during the intensive care unit (ICU) stay, combined EN and parenteral nutrition (PN) may represent an effective and safe option to achieve energy and protein goals as recommended by international guidelines. We hypothesise that critically ill patients at high nutritional risk may benefit from such a combined approach during their stay on the ICU. Therefore, we aim to test if an early combination of EN and high-protein PN (EN+PN) is effective in reaching energy and protein goals in patients at high nutritional risk, while avoiding overfeeding. This approach will be tested in the here-presented EFFORTcombo trial. Nutritionally high-risk ICU patients will be randomised to either high (≥2·2 g/kg per d) or low protein (≤1·2 g/kg per d). In the high protein group, the patients will receive EN+PN; in the low protein group, patients will be given EN alone. EN will be started in accordance with international guidelines in both groups. Efforts will be made to reach nutrition goals within 48-96 h. The efficacy of the proposed nutritional strategy will be tested as an innovative approach by functional outcomes at ICU and hospital discharge, as well as at a 6-month follow-up.

Perioperative non-invasive versus semi-invasive cardiac index monitoring in patients with bariatric surgery - a prospective observational study.

BACKGROUND: In morbidly obese patients undergoing laparoscopic bariatric surgery, the combination of obesity-related comorbidities, pneumoperitoneum and extreme posture changes constitutes a high risk of perioperative hemodynamic complications. Thus, an advanced hemodynamic monitoring including continuous cardiac index (CI) assessment is desirable. While invasive catheterization may bear technical difficulties, transesophageal echocardiography is contraindicated due to the surgical procedure. Evidence on the clinical reliability of alternative semi- or non-invasive cardiac monitoring devices is limited. The aim was to compare the non-invasive vascular unloading to a semi-invasive pulse contour analysis reference technique for continuous CI measurements in bariatric surgical patients. METHODS: This prospective observational study included adult patients scheduled for elective, laparoscopic bariatric surgery after obtained institutional ethics approval and written informed consent. CI measurements were performed using the vascular unloading technique (Nexfin®) and semi-invasive reference method (FloTrac™). At 10 defined measurement time points, the influence of clinically indicated body posture changes, passive leg raising, fluid bolus administration and pneumoperitoneum was evaluated pre- and intraoperatively. Correlation, Bland-Altman and concordance analyses were performed. RESULTS: Sixty patients (mean BMI 49.2 kg/m2) were enrolled into the study and data from 54 patients could be entered in the final analysis. Baseline CI was 3.2 ± 0.9 and 3.3 ± 0.8 l/min/m2, respectively. Pooled absolute CI values showed a positive correlation (rs = 0.76, P < 0.001) and mean bias of of - 0.16 l/min/m2 (limits of agreement: - 1.48 to 1.15 l/min/m2) between the two methods. Pooled percentage error was 56.51%, missing the criteria of interchangeability (< 30%). Preoperatively, bias ranged from - 0.33 to 0.08 l/min/m2 with wide limits of agreement. Correlation of CI was best (rs = 0.82, P < 0.001) and percentage error lowest (46.34%) during anesthesia and after fluid bolus administration. Intraoperatively, bias ranged from - 0.34 to - 0.03 l/min/m2 with wide limits of agreement. CI measurements correlated best during pneumoperitoneum and after fluid bolus administration (rs = 0.77, P < 0.001; percentage error 35.95%). Trending ability for all 10 measurement points showed a concordance rate of 85.12%, not reaching the predefined Critchley criterion (> 92%). CONCLUSION: Non-invasive as compared to semi-invasive CI measurements did not reach criteria of interchangeability for monitoring absolute and trending values of CI in morbidly obese patients undergoing bariatric surgery. TRIAL REGISTRATION: The study was registered retrospectively on June 12, 2017 with the registration number NCT03184272 .

Video-based, student tutor- versus faculty staff-led ultrasound course for medical students - a prospective randomized study.

BACKGROUND: Ultrasound education is propagated already during medical school due to its diagnostic importance. Courses are usually supervised by experienced faculty staff (FS) with patient bedside examinations or students among each other but often overbooked due to limited FS availability. To overcome this barrier, use of teaching videos may be advantageous. Likewise, peer teaching concepts solely with trained student tutors have shown to be feasible and effective. The aim was to evaluate 1) objective learning outcomes of a combined video-based, student-tutor (ViST) as compared to a FS-led course without media support, 2) acceptance and subjective learning success of the videos. METHODS: Two ultrasound teaching videos for basic and advanced abdominal ultrasound (AU) and transthoracic echocardiography (TTE) were produced and six students trained as tutors. Fourth-year medical students (N = 96) were randomized to either the ViST- or FS course (6 students per tutor). Learning objectives were defined equally for both courses. Acquired practical basic and advanced ultrasound skills were tested in an objective structured clinical examination (OSCE) using modified validated scoring sheets with a maximum total score of 40 points. Acceptance and subjective learning success of both videos were evaluated by questionnaires based on Kirkpatrick's evaluation model with scale-rated closed and open questions. RESULTS: 79 of 96 medical students completed the OSCE and 77 could be finally analyzed. There was no significant difference in the mean total point score of 31.3 in the ViST (N = 42) and 32.7 in the FS course (N = 35, P = 0.31) or in any of the examined basic or advanced ultrasound skill subtasks. Of the 42 ViST participants, 29 completed the AU and 27 the TTE video questionnaire. Acceptance and subjective learning success of both videos was rated positively in 14-52% and 48-88% of the rated responses to each category, respectively. Attendance of either the student or faculty tutor was deemed necessary in addition to the videos. CONCLUSIONS: A ViST versus FS teaching concept was able to effectively teach undergraduate students in AU and TTE, albeit acceptance of the teaching videos alone was limited. However, the ViST concept has the potential to increase course availability and FS resource allocation.

[The New DGEM Guideline - All the Clinician Needs to Know]. / Die neue DGEM-Leitlinie ­ alles, was der Kliniker wissen muss.

The German Society for Nutritional Medicine has recently updated its guideline on clinical nutrition in critically ill patients thereby cooperating with seven other national medical societies. This article provides readers with a concise overview on selected key aspects of this guideline relevant for clinical practice. We will discuss some issues in detail such as the determination of energy expenditure and of calorie and protein intake, the choice of the route of administration (enteral or parenteral), and the handling of micronutrients.

[Nutrition in Critically Ill Patients - Challenges in Special Patient Groups]. / Ernährung des Intensivpatienten: Herausforderung bei besonderen Patientengruppen.

Medical nutrition therapy in daily intensive care often is challenging for the clinician. The severity of disease with possible compromises of conscience, hemodynamics, respiration, renal and gastrointestinal systems requires an individual adaptation of the nutrient-supply adjusted to the disease phase and secondary metabolic tolerance. For these adjustments, clinicians should consider the nature of the acute disease leading to critical illness and also the preceding nutrition state, comorbidities and demographics, as well as the prognosis of the patient. Close monitoring is necessary for a rapid response in case the medical condition changes or new medical or nutritional problems arise.This pragmatic educational article describes recommended nutrition therapies for different patient cohorts in intensive care medicine based on currently valid (inter)national guidelines.

Enteral vs. parenteral nutrition in septic shock: are they equivalent?

PURPOSE OF REVIEW: The current review focuses on recent clinical evidence and updated guideline recommendations on the effects of enteral vs. parenteral nutrition in adult critically ill patients with (septic) shock. RECENT FINDIGS: The largest multicenter randomized-controlled trial showed that the route of nutrient supply was unimportant for 28-day and 90-day mortality, infectious morbidity and length of stay in mechanically ventilated patients with shock. The enteral route, however, was associated with lower macronutrient intake and significantly higher frequency of hypoglycemia and moderate-to-severe gastrointestinal complications. Integrating these findings into recent meta-analyses confirmed that the route per se has no effect on mortality and that interactions with (infectious) morbidity are inconsistent or questionable. SUMMARY: The strong paradigm of favoring the enteral over the parenteral route in critically ill patients has been challenged. As a consequence, updated guidelines recommend withholding enteral nutrition in patients with uncontrolled shock. It is still unclear, however, whether parenteral nutrition is advantageous in patients with shock although benefits are conceivable in light of less gastrointestinal complications. Thus far, no guideline has addressed indications for parenteral nutrition in these patients. By considering recent scientific evidence, specific guideline recommendations, and expert opinions, we present a clinical algorithm that may facilitate decision-making when feeding critically ill patients with shock.

Metabolic support in the critically ill: a consensus of 19.

Metabolic alterations in the critically ill have been studied for more than a century, but the heterogeneity of the critically ill patient population, the varying duration and severity of the acute phase of illness, and the many confounding factors have hindered progress in the field. These factors may explain why management of metabolic alterations and related conditions in critically ill patients has for many years been guided by recommendations based essentially on expert opinion. Over the last decade, a number of randomized controlled trials have been conducted, providing us with important population-level evidence that refutes several longstanding paradigms. However, between-patient variation means there is still substantial uncertainty when translating population-level evidence to individuals. A cornerstone of metabolic care is nutrition, for which there is a multifold of published guidelines that agree on many issues but disagree on others. Using a series of nine questions, we provide a review of the latest data in this field and a background to promote efforts to address the need for international consistency in recommendations related to the metabolic care of the critically ill patient. Our purpose is not to replace existing guidelines, but to comment on differences and add perspective.

[DGEM Guideline "Clinical Nutrition in Critical Care Medicine" - short version]. / DGEM-Leitlinie: Klinische Ernährung in der Intensivmedizin ­ Kurzversion.

PURPOSE: Variations of clinical nutrition may affect outcome of critically ill patients. Here we present the short version of the updated consenus-based guideline (S2k classification) "Clinical nutrition in critical care medicine" of the German Society for Nutritional Medicine (DGEM) in cooperation with 7 other national societies. The target population of the guideline was defined as critically ill adult patients who suffer from at least one acute organ dysfunction requiring specific drug therapy and/or a mechanical support device (e.g. mechanical ventilation) to maintain organ function. METHODS: The former guidelines of the German Society for Nutritional Medicine (DGEM) were updated according to the current instructions of the Association of the Scientific Medical Societies in Germany (AWMF) valid for a S2k-guideline. We considered and commented the evidence from randomized-controlled trials, meta-analyses and observational studies with adequate sample size and high methodological quality (until May 2018) as well as from currently valid guidelines of international societies. The liability of each recommendation was indicated using linguistic terms. Each recommendation was finally validated and consented by a Delphi process. RESULTS: The short version presents a summary of all 69 consented recommendations for essential, practice-relevant elements of clinical nutrition in the target population. A specific focus is the adjustment of nutrition according to the phases of critical illness, and to the individual tolerance to exogenous substrates. Among others, recommendations include the assessment of nutritional status, the indication for clinical nutrition, the timing, route, magnitude and composition of nutrition (macro- and micronutrients) as well as distinctive aspects of nutrition therapy in obese critically ill patients and those with extracorporeal support devices. CONCLUSION: The current short version of the guideline provides a concise summary of the updated recommendations for enteral and parenteral nutrition of adult critically ill patients who suffer from at least one acute organ dysfunction requiring pharmacological and/or mechanical support. The validity of the guideline is approximately fixed at five years (2018 - 2023).

Nutritional support in patients with extracorporeal life support and ventricular assist devices.

PURPOSE OF REVIEW: Extracorporeal life support (ECLS) including venovenous and venoarterial extracorporeal membrane oxygenation (ECMO) and ventricular assist devices (VAD) provide mechanical pulmonary and circulatory support, respectively, in patients with acute pulmonary or cardiovascular failure. This review discusses recently published data regarding specific topics of nutritional support in patients with ECLS and VAD. RECENT FINDINGS: ECLS may aggravate loss of endogenous and exogenous micronutrients and macronutrients. Observational studies have shown that enteral nutrition is feasible and most commonly used in patients with ECLS. Indirect calorimetry may be feasible for measuring energy expenditure during ECLS. Specific tools are available to assess malnutrition or nutrition risk in patients with VAD but require further validation in the perioperative setting. If parenteral nutrition is indicated, the use of intravenous lipid emulsions may be associated with membrane oxygenator dysfunction of the ECLS device or increased infectious risk in patients with VAD. SUMMARY: Despite the exponential use of ECLS and VAD over the last decade, the role of nutrition on clinical outcome in this patient population remains an important but yet underinvestigated field.